Diabetes mellitus (DM) and multi-vessel coronary artery disease (CAD) entail significant risk for progression of cardiac morbidity and mortality. Compelling recent research links androgen deficiency (AD) and erectile dysfunction (ED) in men to DM and CAD. We hypothesize that AD and ED independently serve as sentinel indicators, predicting the future development of adverse cardiovascular and cerebrovascular events in men with diabetes following [percutaneous coronary intervention (PCI)]. A unique opportunity to test these hypotheses is presented by the Future REvascularization Evaluation in patients with Diabetes mellitus: Optimal management of Multivessel disease (FREEDOM) study. This NHLBI sponsored study is a multi-institutional randomized controlled trial comparing revascularization with either coronary artery bypass graft surgery (CABG) or with drug eluting stents in 2,400 patients with DM and multi-vessel CAD. Specific aims of this ancillary study are: (1) To determine whether androgen status at baseline independently predicts FREEDOM Trial primary and secondary endpoints in men (n=1143) enrolled in the [FREEDOM Trial New York Cohort]. (2) To determine whether sexual function at baseline independently predicts cardiovascular outcomes in men enrolled in the [FREEDOM Trial New York Cohort]. (3) To determine whether change of androgen status and sexual function over time independently predict cardiovascular outcomes in men enrolled in the [FREEDOM Trial New York Cohort] and (4) To demonstrate specific mediators and pathways that link sexual function and androgen status to cardiovascular disease. This ancillary study will examine specific mediating pathways relating AD and ED to cardiac outcome, thereby testing the predictions of our theoretical framework. We propose that ED is a marker of endothelial dysfunction i.e. that severe ED correlates with poor endothelial function, and predicts poor cardiac prognosis. We also propose that AD affects endothelial function in men with DM and CAD directly and through its influence on the presentation and progression of inflammation and hemostasis. We anticipate that the results of our research will significantly enhance the scientific knowledge of the relationship between ED, AD, and cardiovascular disease. Our findings may encourage diagnostic testing of ED and AD in clinical practice, leading to early detection and improved prevention of cardiovascular disease in at-risk groups. This study may also encourage the use of existing interventions for ED and AD as potential treatments that improve cardiovascular outcomes for men with DM and CAD. Finally, the biological pathways identified in this study may identify early predictors and suggest new therapeutic targets for the development of novel treatments for cardiovascular disease. Public Health Relevance: (provided by the applicant): The results of this ancillary study may encourage diagnostic testing of erectile dysfunction (ED) and androgen status (AS) in clinical practice, leading to improved prevention of cardiovascular disease in at-risk groups. This study may also encourage the use of existing interventions for ED and AS as treatments to improve cardiovascular outcomes for men with diabetes mellitus and coronary artery disease. Finally, the biological pathways identified this study may suggest new therapeutic targets and aid the development of novel treatments for cardiovascular disease.